Hi. This is to anyone who has ever observed the same. We found a large Indel (400bp) within a known gene. When the insertion is not present (deletion), the gene is expressed (like a functional version of the gene). But when the insertion is present, there is a SNP within the inserted sequence that can also be correlated with the expression. Something like this:
Deletion --> expresion
Insertion: SNP A within insertion --> expression
Insertion: SNP T within insertion --> No expression
The correlation between deletion/expression could be explained as a functional version, and the insertion could disrupt the gene, so it should be non functional (like many transposons do). But having expression even with the insertion, but only when a specific SNP is present, is confusing to me.
I would appreciate any suggestion to find a biological explanation for this results.
Thank you!
Are you certain that there is no other change present (particularly upstream, in promoter or other cis-regulatory elements, etc.) in the individuals with "SNP T" insertions?
I've never heard about this before... so interesting! I am curious about it.
Is the insertion inside an intron? If yes, splicing variants could explain the expression of the gene. The SNP might be differently recognized by the spliceosome. Did you try to compare (in RT-qPCR) the melting curves of the two transcripts? Jack is also right, other polymorphisms in promoter regions might explain this issue.
Thank you for the answers! Certainly, Jack, I forgot to mention that these Indel and SNP are present within the 5'UTR region. So I'm trying to find a biological explanation regarding regulatory elements (whether the SNP makes this sequence an inhibitor of expression...). Regards,
Thanks Fabiano. This could be the explanation, but I can't find any regulatory elements in any database. How could I tell this without any evidence? Regarding the qRT, we Sanger-sequenced both transcripts, and the splicing looks the same, although the fold change among them is around 40.
Hello Jose. How did you design the RT-qPCR primers? Where exactly do these primers flank and what's the size of the amplicon? Does the RT-qPCR primer flank the SNP position?
Hi. The primers don't flank the snp since it is within the UTR and the primers are designed in an exon.
Hi Jose
Do you try these database?
Jiang, C., et al. "TRED: a transcriptional regulatory element database, new entries and other development." Nucleic acids research 35.suppl 1 (2007): D137-D140.
Sebastian, Alvaro, and Bruno Contreras-Moreira. "footprintDB: a database of transcription factors with annotated cis elements and binding interfaces." Bioinformatics (2013): btt663.
If you work on plants:
Lescot, Magali, et al. "PlantCARE, a database of plant cis-acting regulatory elements and a portal to tools for in silico analysis of promoter sequences." Nucleic acids research 30.1 (2002): 325-327.
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